tbuckley/cabot-search huggingface dataset:
Letter to the editor: Cautious interpretation of the compensation of insulin‐mTORC1 activation to promote liver regeneration in the absence of hepatocyte β‐catenin
Authors: Cong Ning, Xin‐Mu Zhang, Xin‐Ting Sang, Hai‐Tao Zhao
Journal: Hepatology (2022)

To the editor, We followed with interest the report by Shikai et al. on the underlying mechanisms driving liver regeneration (LR).1 This study concluded that the compensatory activation of the insulin‐mammalian target of rapamycin complex 1 (mTORC1) promoted LR in the absence of hepatocyte β‐catenin. We appreciated the authors' tremendous amount of work; however, some important issues required more explanation, especially because of the multiple internal pathways and complex mechanisms in LR. Mammalian target of rapamycin is a protein kinase that regulates cell growth, proliferation, and survival, as well as transcription and protein synthesis. A previous study has suggested the essential roles of mTORC1 in cell proliferation during LR in zebrafish.2 Raptor exists in mTORC1 as one of the specific binding partners. In this study, Raptor‐deficient mice did not provide a sufficient time window following partial hepatectomy (PH) to observe the process of LR, especially in double‐deletion mice that demised 12 h following PH. The function of Raptor might be too powerful to mask the regulatory role of β‐catenin in liver homeostasis and regeneration, and the compensatory or cooperative relationship between the mTORC1 and β‐catenin should be interpreted more cautiously. Second, Nadejda et al. identified mTORC1 as a major regulator of pancreatic α cell mass and glucagon secretion,3 which might explain the observed significant reduction in serum glucose in RaptorΔHC mice compared with control at 2 weeks after virus injection to some extent. Could the acute death of RaptorΔHC mice after PH be caused by hypoglycemia? It is necessary to monitor the level of post‐PH serum glucose, which might help improve the survival rate of gene‐edited mice. Third, in this study, the sequence of screening downstream products of β‐catenin and other pathways regulating LR was chaotic. It is suggested to improve the experimental flow chart, which might make the conclusion of the research more logical and persuasive, as there are many noncanonical signaling pathways in the liver that affect hepatocellular proliferation including Wnt/STOP and Wnt/TOR pathways.4 In addition, the sample size of some experiments was small or vague, which might threaten the reproducibility of this study. In conclusion, this study provided a potential therapeutic target for LR after acute liver injury or hepatectomy. However, a more logical research design is needed to improve translational value.
Artificial intelligence (AI)-based decision support improves reproducibility of tumor response assessment in neuro-oncology: An international multi-reader study
Authors: Philipp Vollmuth, Martha Foltyn, Raymond Y Huang, Norbert Galldiks, Jens Petersen, Fabian Isensee, Martin J van den Bent, Frederik Barkhof, Ji Eun Park, Yae Won Park, Sung Soo Ahn, Gianluca Brugnara, Hagen Meredig, Rajan Jain, Marion Smits, Whitney B Pope, Klaus Maier-Hein, Michael Weller, Patrick Y Wen, Wolfgang Wick, Martin Bendszus
Journal: Neuro-Oncology (2022)

Abstract Background To assess whether artificial intelligence (AI)-based decision support allows more reproducible and standardized assessment of treatment response on MRI in neuro-oncology as compared to manual 2-dimensional measurements of tumor burden using the Response Assessment in Neuro-Oncology (RANO) criteria. Methods A series of 30 patients (15 lower-grade gliomas, 15 glioblastoma) with availability of consecutive MRI scans was selected. The time to progression (TTP) on MRI was separately evaluated for each patient by 15 investigators over two rounds. In the first round the TTP was evaluated based on the RANO criteria, whereas in the second round the TTP was evaluated by incorporating additional information from AI-enhanced MRI sequences depicting the longitudinal changes in tumor volumes. The agreement of the TTP measurements between investigators was evaluated using concordance correlation coefficients (CCC) with confidence intervals (CI) and P-values obtained using bootstrap resampling. Results The CCC of TTP-measurements between investigators was 0.77 (95% CI = 0.69,0.88) with RANO alone and increased to 0.91 (95% CI = 0.82,0.95) with AI-based decision support (P = .005). This effect was significantly greater (P = .008) for patients with lower-grade gliomas (CCC = 0.70 [95% CI = 0.56,0.85] without vs. 0.90 [95% CI = 0.76,0.95] with AI-based decision support) as compared to glioblastoma (CCC = 0.83 [95% CI = 0.75,0.92] without vs. 0.86 [95% CI = 0.78,0.93] with AI-based decision support). Investigators with less years of experience judged the AI-based decision as more helpful (P = .02). Conclusions AI-based decision support has the potential to yield more reproducible and standardized assessment of treatment response in neuro-oncology as compared to manual 2-dimensional measurements of tumor burden, particularly in patients with lower-grade gliomas. A fully-functional version of this AI-based processing pipeline is provided as open-source (https://github.com/NeuroAI-HD/HD-GLIO-XNAT).
BTApep-TAT peptide inhibits ADP-ribosylation of BORIS to induce DNA damage in cancer
Authors: Yanmei Zhang, Mengdie Fang, Shouye Li, Hao Xu, Juan Ren, Linglan Tu, Bowen Zuo, Wanxin Yao, Guang Liang
Journal: Molecular Cancer (2022)

Brother of regulator of imprinted sites (BORIS) is expressed in most cancers and often associated with short survival and poor prognosis in patients. BORIS inhibits apoptosis and promotes proliferation of cancer cells. However, its mechanism of action has not been elucidated, and there is no known inhibitor of BORIS.A phage display library was used to find the BORIS inhibitory peptides and BTApep-TAT was identified. The RNA sequencing profile of BTApep-TAT-treated H1299 cells was compared with that of BORIS-knockdown cells. Antitumor activity of BTApep-TAT was evaluated in a non-small cell lung cancer (NSCLC) xenograft mouse model. BTApep-TAT was also used to investigate the post-translational modification (PTM) of BORIS and the role of BORIS in DNA damage repair. Site-directed mutants of BORIS were constructed and used for investigating PTM and the function of BORIS.BTApep-TAT induced DNA damage in cancer cells and suppressed NSCLC xenograft tumor progression. Investigation of the mechanism of action of BTApep-TAT demonstrated that BORIS underwent ADP ribosylation upon double- or single-strand DNA damage. Substitution of five conserved glutamic acid (E) residues with alanine residues (A) between amino acids (AAs) 198 and 228 of BORIS reduced its ADP ribosylation. Inhibition of ADP ribosylation of BORIS by a site-specific mutation or by BTApep-TAT treatment blocked its interaction with Ku70 and impaired the function of BORIS in DNA damage repair.The present study identified an inhibitor of BORIS, highlighted the importance of ADP ribosylation of BORIS, and revealed a novel function of BORIS in DNA damage repair. The present work provides a practical method for the future screening or optimization of drugs targeting BORIS.
Impact of health and lifestyle food supplements on periodontal tissues and health
Authors: Axel Spahr, Tihana Divnic‐Resnik
Journal: Periodontology 2000 (2022)

According to the new classification, periodontitis is defined as a chronic multifactorial inflammatory disease associated with dysbiotic biofilms and characterized by progressive destruction of the tooth-supporting apparatus. This definition, based on the current scientific evidence, clearly indicates and emphasizes, beside the microbial component dental biofilm, the importance of the inflammatory reaction in the progressive destruction of periodontal tissues. The idea to modulate this inflammatory reaction in order to decrease or even cease the progressive destruction was, therefore, a logical consequence. Attempts to achieve this goal involve various kinds of anti-inflammatory drugs or medications. However, there is also an increasing effort in using food supplements or so-called natural food ingredients to modulate patients' immune responses and maybe even improve the healing of periodontal tissues. The aim of this chapter of Periodontology 2000 is to review the evidence of various food supplements and ingredients regarding their possible effects on periodontal inflammation and wound healing. This review may help researchers and clinicians to evaluate the current evidence and to stimulate further research in this area.
Selected Articles from This Issue
Journal: Clinical Cancer Research (2022)

Effective systemic treatment options are largely limited for previously treated liposarcoma and leiomyosarcoma.In this phase II study, Kim and colleagues show that eribulin-gemcitabine combination therapy demonstrated appreciable efficacy compared to monotherapy from the historic arm.Functional enrichment in the transforming growth factor-ß pathway would hold predictive value for the survival outcomes of the combination therapy, although further confirmatory investigation may be required.Eribulin-gemcitabine combination therapy could present as a future treatment option for refractory soft tissue sarcomas with liposarcoma or leiomyosarcoma histology.
Rethinking Fetal Personhood in Conceptualizing Roe
Authors: Rosemarie Garland-Thomson, Joel Michael Reynolds
Journal: The American Journal of Bioethics (2022)

This article refers to:The End of Roe v. WadeBeyond Abortion: The Consequences of Overturning RoeThe Ethics of Access: Reframing the Need for Abortion Care as a Health Disparity
CircIPO7 Promotes Nasopharyngeal Carcinoma Metastasis and Cisplatin Chemoresistance by Facilitating YBX1 Nuclear Localization
Authors: Xiaohong Hong, Qian Li, Junyan Li, Kailin Chen, Qingmei He, Yuheng Zhao, Yelin Liang, Yin Zhao, Han Qiao, Na Liu, Jun Ma, Yingqin Li
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Cisplatin-based chemotherapy effectively improves the distant-metastasis control in nasopharyngeal carcinoma (NPC), but approximately 30% of patients develop treatment failure due to chemoresistance. However, the underlying mechanisms remain poorly understood. Experimental Design: Circular RNA (circRNA) sequencing data were used to identify metastasis-specific circRNAs and the expression of circIPO7 was validated in NPC tissues as well as NPC cell lines by qRT-PCR. The whole transcriptional profile upon circIPO7 knockdown was applied to explore the biological function and regulatory mechanism, which were further confirmed by in vitro and in vivo metastasis/chemosensitivity assays. We also evaluated the value of circIPO7 expression in predicting NPC metastasis and cisplatin chemoresistance by analyzing a cohort of 183 NPC patients. Results: In this study, circIPO7, a novel circRNA, is found to be specifically overexpressed in NPC patients with distant metastasis. Knockdown of circIPO7 in NPC cells suppresses their metastasis and increases sensitivity to cisplatin treatment in vitro and in vivo. Mechanistically, circIPO7 binds to Y-box binding protein-1 (YBX1) protein in the cytoplasm and facilitates its phosphorylation at serine 102 (p-YBX1S102) by the kinase AKT, which further promotes YBX1 nuclear translocation and activates FGFR1, TNC, and NTRK1 transcription. Clinically, higher circIPO7 expression indicates unfavorable distant metastasis-free survival in NPC patients given cisplatin-based chemotherapy. Conclusions: Altogether, this study identifies oncogenic circIPO7 as a prognostic marker after cisplatin-based chemotherapy and as a potential therapeutic target for overcoming metastasis and chemoresistance in NPC.
<scp>Drug‐associated</scp> bone resorption with potential dental and implant implications
Authors: Georgios E. Romanos, Michael Vaglica, Anton Sculean
Journal: Periodontology 2000 (2022)

Abstract Every year more and more innovative pharmacological agents are introduced medicine, to treat systemic diseases. Due to these rapid and recent advancements, many patients are receiving treatment with a high variety of drugs, such as selective serotonin reuptake inhibitors, bisphosphonates, tumor necrosis factor (TNF)‐α inhibitors, cyclosporine, and steroids. Since implant and osseous surgery are common treatment modalities used, within dentistry, it is of critical important to acknowledge and discuss the potential effects of selective serotonin reuptake inhibitors, bisphosphonates, TNF‐α inhibitors, cyclosporine, and steroids, on bone healing. The present paper discusses the possible detrimental ramifications and risks these drug classes may have on bone healing.
Ventricular arrhythmias and sudden death events following acalabrutinib initiation
Authors: Seema A. Bhat, John Gambril, Leylah Azali, Sunnia T. Chen, Lindsay Rosen, Marilly Palettas, Tracy E. Wiczer, Sujay Kalathoor, Qiuhong Zhao, Kerry A. Rogers, Adam Kittai, Michael Grever, Farrukh Awan, Patrick Ruz, John C. Byrd, Jennifer Woyach, Daniel Addison
Journal: Blood (2022)
Selenium Modulates Cancer Cell Response to Pharmacologic Ascorbate
Authors: Connor S.R. Jankowski, Joshua D. Rabinowitz
Journal: Cancer Research (2022)

High-dose ascorbate (vitamin C) has shown promising anticancer activity. Two redox mechanisms have been proposed: hydrogen peroxide generation by ascorbate itself or glutathione depletion by dehydroascorbate (formed by ascorbate oxidation). Here we show that the metabolic effects and cytotoxicity of high-dose ascorbate in vitro result from hydrogen peroxide independently of dehydroascorbate. These effects were suppressed by selenium through antioxidant selenoenzymes including glutathione peroxidase 1 (GPX1) but not the classic ferroptosis-inhibiting selenoenzyme GPX4. Selenium-mediated protection from ascorbate was powered by NADPH from the pentose phosphate pathway. In vivo, dietary selenium deficiency resulted in significant enhancement of ascorbate activity against glioblastoma xenografts. These data establish selenoproteins as key mediators of cancer redox homeostasis. Cancer sensitivity to free radical-inducing therapies, including ascorbate, may depend on selenium, providing a dietary approach for improving their anticancer efficacy.
Complications and treatment errors in periodontal and implant therapy
Authors: Giovanni Zucchelli, Hom‐Lay Wang, Leandro Chambrone
Journal: Periodontology 2000 (2022)

Abstract The assortment of periodontal and implant‐related treatments has been continuously improved over the last 50 years. Once the decision‐making process has been established and the treatment procedure applied, the partial or complete resolution of the problem (eg, periodontal probing depth reduction, clinical attachment level gain, gingival recession reduction, dental hypersensitivity decrease) and a diagnosis change with no or minimal occurrence of adverse events (ie, complications, harms, technical errors, or adverse/side effects) can be expected. The clear identification of the potential types of adverse effects, complications, or even errors is important for contemporary decision‐making processes, as they may be related to different local, systemic, and technical aspects. This chapter focused on four core components: (a) providing periodontal definitions for errors, complications, harms, and side effects; (b) defining the types of risk and the clinical impact of adverse effects, errors, and complications in periodontal and peri‐implant therapies; (c) evaluating the influence of accidental errors versus the lack of a proper treatment planning; and (d) reporting on the importance of establishing the “net benefit ratio” between the clinical improvements promoted by the therapy and the occurrence of potential adverse events.
Transcription Factors YAP/TAZ and SRF Cooperate To Specify Renal Myofibroblasts in the Developing Mouse Kidney
Authors: Keri A. Drake, Christopher Chaney, Mohita Patel, Amrita Das, Julia Bittencourt, Martin Cohn, Thomas J. Carroll
Journal: Journal of the American Society of Nephrology (2022)

The embryonic renal stroma consists of multiple molecularly distinct cell subpopulations, the functional significance of which is largely unknown. Previous work has demonstrated that the transcription factors YAP and TAZ play roles in the development and morphogenesis of the nephrons, collecting ducts, and nephron progenitor cells.
Inflammation as a link between periodontal disease and obesity
Authors: Ferda Pamuk, Alpdogan Kantarci
Journal: Periodontology 2000 (2022)

Abstract Nutrition plays a critical role in the homeostatic balance, maintenance of health, and longevity. There is a close link between inflammatory diseases and nutritional health. Obesity is a severe pathological process with grave implications on several organ systems and disease processes, including type 2 diabetes, cardiovascular disease, osteoarthritis, and rheumatoid arthritis. The impact of obesity on periodontal inflammation has not been fully understood; the association between nutritional balance and periodontal inflammation is much less explored. This review is focused on the potential mechanistic links between periodontal diseases and obesity and common inflammatory activity pathways that can be pharmacologically targeted.
Care Quality for Patients with Chronic Obstructive Pulmonary Disease in the Readmission Penalty Era
Authors: Juan C. Rojas, Sukarn Chokkara, Mengqi Zhu, Peter K. Lindenauer, Valerie G. Press
Journal: American Journal of Respiratory and Critical Care Medicine (2022)

Chronic obstructive pulmonary disease (COPD) is the fifth-leading cause of admissions and third-leading cause of readmissions among U.S. adults. Recent policies instituted financial penalties for excessive COPD readmissions.
Periodontitis and peri‐implantitis in elderly people experiencing institutional and hospital confinement
Authors: Frauke Müller, Murali Srinivasan, Karl‐Heinz Krause, Martin Schimmel
Journal: Periodontology 2000 (2022)

An increasing number of elderly people retain their natural teeth into old age and further, the prevalence of endosseous implants for supporting oral prosthesis is ever increasing. These teeth and implants now present a considerable challenge in terms of maintenance, especially when patients become dependent on care. Periodontal and peri-implant diseases are more prevalent in elderly than in younger age cohorts. There are distinct differences related to the inflammatory response between periodontal and peri-implant tissues, both in young and old age. The age-related reasons for the increase in periodontal infections may be related to poor oral hygiene because of a loss of dexterity or vision, but also to immunosenescence. This term describes the aging of the immune system and the decline of its effectiveness with age. Low-grade infections, like chronic periodontitis, may cause low-grade inflammation and subsequently increase the likelihood of developing chronic diseases. In return, treatment of periodontitis may improve general health, as demonstrated for diabetes. A second mechanism illustrating how poor oral health translates into systemic disease is the risk of developing aspiration pneumonia. The treatment options in old age should be evaluated with regard to the issues of general health and maintenance. Systematic periodontal maintenance therapy, as performed in younger age cohorts, may be difficult to implement in elderly people experiencing institutional or hospital confinement because of logistics, barriers related to patients and caregivers, or cost. The scale of periodontal disease in old age represents a public health issue.
Multinational Federated Learning Approach to Train ECG and Echocardiogram Models for Hypertrophic Cardiomyopathy Detection
Authors: Shinichi Goto, Divyarajsinhji Solanki, Jenine E. John, Ryuichiro Yagi, Max Homilius, Genki Ichihara, Yoshinori Katsumata, Hanna K. Gaggin, Yuji Itabashi, Calum A. MacRae, Rahul C. Deo
Journal: Circulation (2022)

Background: Novel targeted treatments increase the need for prompt hypertrophic cardiomyopathy (HCM) detection. However, its low prevalence (0.5%) and resemblance to common diseases present challenges that may benefit from automated machine learning–based approaches. We aimed to develop machine learning models to detect HCM and to differentiate it from other cardiac conditions using ECGs and echocardiograms, with robust generalizability across multiple cohorts. Methods: Single-institution HCM ECG models were trained and validated on external data. Multi-institution models for ECG and echocardiogram were trained on data from 3 academic medical centers in the United States and Japan using a federated learning approach, which enables training on distributed data without data sharing. Models were validated on held-out test sets for each institution and from a fourth academic medical center and were further evaluated for discrimination of HCM from aortic stenosis, hypertension, and cardiac amyloidosis. Last, automated detection was compared with manual interpretation by 3 cardiologists on a data set with a realistic HCM prevalence. Results: We identified 74 376 ECGs for 56 129 patients and 8392 echocardiograms for 6825 patients at the 4 academic medical centers. Although ECG models trained on data from each institution displayed excellent discrimination of HCM on internal test data (C statistics, 0.88–0.93), the generalizability was limited, most notably for a model trained in Japan and tested in the United States (C statistic, 0.79–0.82). When trained in a federated manner, discrimination of HCM was excellent across all institutions (C statistics, 0.90–0.96 and 0.90–0.96 for ECG and echocardiogram model, respectively), including for phenotypic subgroups. The models further discriminated HCM from hypertension, aortic stenosis, and cardiac amyloidosis (C statistics, 0.84, 0.83, and 0.88, respectively, for ECG and 0.93, 0.94, 0.85, respectively, for echocardiogram). Analysis of electrocardiography-echocardiography paired data from 11 823 patients from an external institution indicated a higher sensitivity of automated HCM detection at a given positive predictive value compared with cardiologists (0.98 versus 0.81 at a positive predictive value of 0.01 for ECG and 0.78 versus 0.59 at a positive predictive value of 0.24 for echocardiogram). Conclusions: Federated learning improved the generalizability of models that use ECGs and echocardiograms to detect and differentiate HCM from other causes of hypertrophy compared with training within a single institution.